Marie-Noëlle Ungeheuer

• Pasteur Network

Background Gastric cancer (GC) is often associated with a poor prognosis, due to its asymptomatic early stages. The current gold standard for diagnosing GC, upper endoscopy, is invasive and has limited sensitivity for detecting gastric preneoplasia such as dysplasia. Non-invasive biomarkers, such as circulating proteins in the blood, hold promise f...

Background Establishing correlates of protection often requires large cohorts. A rapid and adaptable case–control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva. Methods We designed a case–control study to compare antibody lev...

In this multicenter study conducted in France, we challenged the hypothesis of the transmission of pathogens other than Borrelia spp. in 22 patients developing erythema migrans following a tick bite. Using a combination of high-throughput microfluidic PCRs and agnostic metagenomics on skin biopsies and blood samples, no microorganisms other than Bo...

The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluate...

Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC i...

Background The seasonal human coronaviruses (HCoV) NL63, 229E, OC43 and HKU1, are endemic throughout the world, yet the majority of HCoV infections remain undiagnosed. Serology can reliably identify individuals previously infected with HCoVs. Methods In a cross-sectional seroprevalence study, 2,389 serum samples were collected from children and ad...

Background The risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.Methods To correlate antibod...

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two ass...

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. The Modified Vaccinia Ankara (MVA)-based vaccine was used as prophylaxis, but its effectiveness remains poorly characterized. Here, we developed two assays for quantification of neutralizing antibodies (NAbs), using MVA-GFP or a recently isolated MPXV. We measured NAb l...

Background To achieve elimination of Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense (gHAT), the development of highly sensitive diagnostics is needed. We have developed a CRISPR based diagnostic for HAT using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) that is readily adaptable to a field-based sett...

Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Fu...

Background The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised. Methods In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 resident...

Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, and monoclonal antibody explorations revealed humo...

Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment remain yet highly debated. Here we showed that fecal microbiota transplantation (FMT) from aged, but not young, animal donors in young mice is sufficient to trigger profound hippocampal alterations including ast...

The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon β (IFNβ) is a major upstream determinant of IL-12p70 production, which is als...

The dengue virus nonstructural protein 1 (NS1) is a secreted virulence factor that modulates complement, activates immune cells and alters endothelial barriers. The molecular basis of these events remains incompletely understood. Here we describe a functional high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Collap...

Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance in T cell biology is ill defined. APC regulates cytoskeleton organization, cell polarity, and migration in various cell typ...

Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in COVID-19 convalescents combining serological, cellular and monoclonal antibody explorations, revealed humoral im...

The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and ge...

Background The protective immunity against Omicron following a BNT162b2 Pfizer booster dose among elderly is not well characterized. Methods Thirty-eight residents from three nursing homes were recruited for the study. Antibodies targeting the Spike protein of SARS-CoV-2 were measured with the S-Flow assay. Neutralizing activities in sera were mea...

Elimination of Human African Trypanosomiasis (HAT) requires highly specific and sensitive tools for both diagnostic at point of care and epidemiological surveys. We have adapted SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of trypanosome nucleic acids. Our SHERLOCK4HAT diagnostic tool kit, using 7SLRNA, TgSGP...

Background Blood plasma proteins play an important role in immune defense against pathogens, including cytokine signaling, the complement system, and the acute-phase response. Recent large-scale studies have reported genetic (i.e., protein quantitative trait loci, pQTLs) and non-genetic factors, such as age and sex, as major determinants to inter-i...

Introduction: Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. Methods: Two retrospective cohort studies...

Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance for anti-tumor immunity is ill defined. Besides its role in Wnt/β-catenin signaling, APC regulates cytoskeleton organizatio...

Assessment of the cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and extent of the COVID-19 epidemic. Here, we report estimated seroprevalence in the French population and the proportion of infected individuals who developed neutralising antibodies at three points throughout the first epidemic wave. Testing 11,0...

The nonstructural NS1 protein is a virulence factor secreted by dengue virus (DENV)-infected cells. NS1 is known to alter the complement system, activate immune cells and perturb endothelial barriers. Here we show that pro-inflammatory signals are triggered by a high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Ele...

Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 parti...

A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike IgG, IgA and IgM levels with the S-Flow assa...

A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyzed antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike antibody levels with the S-Flow assay and m...

Background Assessment of cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and the extent of the epidemic. As asymptomatic or mild cases were typically not captured by surveillance data in France, we implemented nationwide serological surveillance. We present estimates for prevalence of anti-SARS-CoV-2 antibodies i...

Hidradenitis Suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway (KP) of tr...

Hidradenitis Suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway (KP) of tr...

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals prior to th...

Background The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized. Methods Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% sp...

Background: The extent of SARS-CoV-2 transmission among pupils in primary schools and their families is unknown. Methods: Between 28-30 April 2020, a retrospective cohort study was conducted among pupils, their parents and relatives, and staff of primary schools exposed to SARS-CoV-2 in February and March 2020 in a city north of Paris, France. Part...

Head and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75–80% of cases. In addition to th...

Hidradenitis Suppurativa (HS) is a chronic inflammatory disease of the skin associated with specific lesional dysbiotic features. We studied the microbiome of clinically unaffected typical HS sites (armpits, inguinal folds and gluteal clefts) in 60 HS patients and 17 healthy controls.192 samples obtained by swabbing were analyzed by bacterial cultu...

The ICAReB platform of Institut Pasteur provides access to human bio-resources for academic and private research teams worldwide, essentially in the fields of infection, immunity and neurosciences. More than 134,000 human quality controlled, duly annotated samples (mainly whole-blood derived products, but also stool, urine, saliva, swabs….), from b...

9TH CONFERENCE OF THE EUROPEAN HIDRADENITIS SUPPURATIVA FOUNDATION - ATHENS

Background: Severe Hurley stage 1 Hidradenitis suppurativa (HS1) is a difficult to treat form of the disease. Objective: To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily) - moxifloxacin (400 mg once daily) - metronidazole (250 to 500 mg t.i.d) (RMoM) treatment strategy in severe HS1 patients. Methods...

Background: Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors. Methods: MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (a...

Burning mouth syndrome (BMS) is a poorly understood condition affecting mainly women at menopause with anxiodepressive background. Oral pain is the main symptom although taste and salivary disturbances are also often experienced, suggesting involvement of local factors. Opiorphin produced by submandibulary glands is a natural inhibitor of the neutr...

We evaluated a dipstick test for rapid detection of Shigella sonnei on bacterial colonies, directly on stools and from rectal swabs because in actual field situations, most pathologic specimens for diagnosis correspond to stool samples or rectal swabs. The test is based on the detection of S. sonnei lipopolysaccharide (LPS) O-side chains using phas...

Background: Opiorphin is an endogenous human peptide regulator of enkephalin bioavailability. It inhibits enkephalin-inactivating ectopeptidases to produce analgesia and antidepressant-like effects in standard rodent models via activation of μ and/or δ opioid pathways. Our aim was to establish the quantitative profile of secretion and distribution...

Background: Resequencing DNA microarray (RMA) technology uses probes designed to identify a panel of viral sequences. It can be used for detecting emerging viruses by revealing the nucleotide polymorphisms within the target of interest. Objectives/study design: As a new tool for molecular diagnosis of arbovirus infection, high density PathogenID...

Abbreviations: HS, hidradenitis suppurativa

We describe a test for rapid detection of S. dysenteriae 1 in bacterial cultures and in stools, at the bedside of patients. The test is based on the detection of S. dysenteriae 1 lipopolysaccharide (LPS) using serotype 1-specific monoclonal antibodies coupled to gold particles and displayed on a one-step immunochromatographic dipstick. A concentrat...

In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases--tetanus, diphtheria and pertussis--among 331 adults (aged 18-60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of...

Mammalian zinc ectopeptidases play important roles in turning off neural and hormonal peptide signals at the cell surface, notably those processing sensory information. We report here the discovery of a previously uncharacterized physiological inhibitor of enkephalin-inactivating zinc ectopeptidases in humans, which we have named Opiorphin. It is a...

Helper T lymphocytes that control CD8(+) T-cell and antibody responses are key elements for the resolution of infection by the hepatitis B virus and for the development of effective immunological memory after hepatitis B vaccination. We have used H-2 class II-deficient mice that express the human MHC class II molecule, HLA-DR1, to identify novel he...

The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation--left splenopancreatectomy for beni...

In order to understand natural resistance to filariasis, we compared Litomosoides sigmodontis primary infection of C57BL/6 mice, which eliminate the worms before patency, and BALB/c mice, in which worms complete their development and produce microfilariae. Our analysis over the first month of infection monitoredmigration of the infective larvae fro...

The liver stage of Plasmodium spp. now appears as a relevant target of immune effectors triggered by the so-called "anti-sporozoite" vaccine. Since the monitoring of immune responses at the systemic level may not faithfully reflect the local protective mechanisms, the aim of the present work was to set up a model to study the local intra-hepatic ce...

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous resul...

In order to establish the role of eosinophils in destroying parasites, transgenic mice have been used in experimental helminthiases but not in filariasis. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in transgenic CBA/Ca...

In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days -60, -30 and -15. All animals were cha...

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated chal...

Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding...

For 14 months, effects of volume on blood culture with Bactec 9240 are studied. Amongst the 1392 vials sending a signal out, 15.5% are false positive (FP). They stand out as such true positives by that very fact: negative subcultures, higher blood volumes, shorter time for detection, greater number of aerobic vials. Exclusively for FP, blood volume...